Background The escalating challenges of fine particulate matter (PM_2.5) pollution and global warming pose significant threats to human health. Previous studies have demonstrated that prenatal exposure to PM_2.5 and heat is associated with restricted fetal and offspring growth. However, the combined effects of co-exposure to PM_2.5 and heat remain poorly understood, and the underlying biological mechanisms have yet to be elucidated. Objective To investigate the independent and combined effects of maternal exposure to PM_2.5 and heat on offspring growth and thyroid hormone levels in rats. Methods Eight-week-old SPF Wistar rats were used. Females and males were mated at a 2:1 ratio. After confirming pregnancy, 36 pregnant rats were randomly assigned to four groups: combined PM_2.5 and heat exposure, PM_2.5 exposure, heat exposure, and control. PM_2.5 exposure was administered via intratracheal instillation (0.3 mL, 2 mg·mL⁻¹) daily. Heat exposure was conducted in a programmable constant temperature and humidity chamber maintained at (38.0±1.0)℃ for 1 h daily. Exposures were administered from gestational days (GD) 7 to 13. Offspring were raised for 42 postnatal days (PND), with body weight measured twice weekly at fixed time points. On PND42, blood was collected to separate plasma for the measurement of free triiodothyronine (FT₃) and free thyroxine (FT₄) levels using enzyme-linked immunosorbent assay. Linear mixed-effects models were used to examine the interactive effects of PM_2.5 and heat exposure on offspring body weight and weight gain. One-way analysis of variance was conducted to compare the differences in offspring body weight at each time point and thyroid hormone levels among groups. Correlations between thyroid hormone levels and weight changes were assessed using Spearman's rank correlation analysis. Results Both prenatal PM_2.5 exposure alone and its combination with heat exposure were associated with higher offspring body weight at specific postnatal time points. Offspring in the PM_2.5 exposure group had higher body weight than controls on PND7 and PND21, while those in the combined exposure group had higher body weight on PND7 and PND21-35 (P<0.05), and this effect was stronger in female offspring. The heat exposure group showed significantly lower birth weight than other groups (P<0.05), but this difference gradually disappeared during development. Plasma FT₃ levels were higher in the PM_2.5 exposure group than in the heat exposure and the control groups (P<0.05), but this difference was statistically significant only in female offspring. Plasma FT3 levels were positively correlated with body weight from PND7 to PND42, with correlation coefficients of 0.316–0.539 in all offspring (P<0.05) and 0.419–0.706 in females (P<0.05), while no significant correlation was observed in males. Conclusion Prenatal exposure to PM_2.5 alone or a combination of PM_2.5 and heat may affect postnatal body weight gain in offspring in a time-dependent manner, with more pronounced effects observed in female offspring. Heat exposure alone leads to reduced early-stage weight followed by a trend toward catch-up growth. The findings suggest a specific role of thyroid hormones in the effects of prenatal PM_2.5 and heat exposure on offspring growth, a relationship that warrants further investigation.

Objective To optimize the extraction process of Xuetong capsules and establish its quality control method. Methods The extraction process was optimized by orthogonal experiment using ethanol reflux method to investigate the effects of different factors on diphenylstilbene, aloin and extraction yield. The content of 5 anthraquinone compounds in Xuetong capsule was determined by HPLC. Results The optimal extraction process was to add 10 times ethanol, with an ethanol concentration of 70%, and extract 3 times, each time for 1 h; 5 components had a good linear relationship with peak area within a certain concentration range, r>0.999 7; The range of sample recovery rate was 93.66%-96.85%, RSD range of 1.48%-1.66%. The content determination results of the 5 components in three batches of Xuetong capsules were （0.632-0.641）, （0.660-0.681）, （1.968-1.991）, （2.547-2.580）, and （1.076-1.101） mg/g. Conclusion The method was accurate, reproducible, and highly feasible, which could be references for producing and improving the quality control standards of Xuetong capsules.

Objective:This study aimed to analyze the prognostic risk factors for hepatoid adenocarcinoma of the stomach (HAS) and construct two nomogram-based clinical prediction models to predict overall survival (OS) and recurrence-free survival (RFS) in patients with HAS.Methods:Data were retrospectively collected from 82 patients (64 males, 18 females; mean age 60.3 ± 9.4 years) who underwent radical gastrectomy and were pathologically diagnosed with gastric hepatoid adenocarcinoma at the First Medical Center of the PLA General Hospital between February 2006 and September 2023. Statistical analyses were conducted using SPSS 25.0 and R 4.3.2. Survival analyses were performed using the Kaplan-Meier method, and univariate analyses were used to identify clinical and pathological factors associated with prognosis. Variables with P<0.05 in the univariate analysis were included in multivariate Cox regression models to identify independent risk factors for OS and RFS. These factors were incorporated into the prediction models to construct nomograms. The discriminatory power of the models was assessed using the area under the curve (AUC) of receiver operating characteristic (ROC) analyses, while calibration curves, decision curve analysis (DCA), and comparisons with the 8th edition of the TNM staging system of the American Joint Committee on Cancer (AJCC) were employed to evaluate model performance. Results:Among the 82 patients, 36 (43.9%) exhibited vascular infiltration, 61 (74.4%) had nerve infiltration, and lymph node metastasis was observed in 60 cases (73.2%). Pathological stages I, II, III, and IV were distributed as 11 (13.4%), 26 (31.7%), 44 (53.7%), and 1 (1.2%) cases, respectively. Inflammatory markers included neutrophil-to-lymphocyte ratio (NLR) ≥ 4.33 in 22 cases (26.8%), platelet-to-lymphocyte ratio (PLR) ≥ 142.2 in 50 cases (61.0%), monocyte-to-lymphocyte ratio (MLR) ≥ 0.411 in 22 cases (26.8%), α-fetoprotein (AFP) ≥ 2.48 μg/L in 64 cases (78.0%), and C-reactive protein (CRP) ≥ 7.506 mg/L in 12 cases (14.6%). Among the 82 patients, 3 cases (3.6%) were lost to follow-up. The median follow-up time was 52 (range: 8–147) months, with a median OS of 61(2–147) months. The 1-year and 3-year OS rates were 78.5% and 58.5%, respectively, while the 1-year and 3-year RFS rates were 77.3% and 60.3%, respectively. Multivariate analysis identified several independent risk factors influencing OS in patients with HAS: advanced pathological stage, MLR ≥ 0.411, AFP ≥ 2.545 μg/L, and CRP ≥ 7.51 mg/L. The hazard ratios (HRs) and 95% confidence intervals (CIs) were as follows: 5.218 (1.230–22.143), 2.610 (1.287–5.294), 2.950 (1.013–8.589), and 2.594 (1.145–5.877), respectively (all P < 0.05). For RFS, advanced pathological stage, PLR ≥ 152.0, and MLR ≥ 0.411 were independent risk factors, with HRs (95% CIs) of 4.735 (1.080–20.760), 3.759 (1.259–11.226), and 2.714 (1.218–6.048), respectively (all P < 0.05). The AUC values for OS prediction at 1 year, 3 years, and 5 years were 0.7765, 0.7525, and 0.7702, respectively. For RFS, the AUC values were 0.7304, 0.8137, and 0.8307 at 1 year, 3 years, and 5 years, respectively. The calibration curves demonstrated strong agreement between nomogram- predicted outcomes and observed survival data. DCA indicated that both TNM staging and the nomogram-based clinical prediction models provided a net positive benefit in predicting OS and RFS in HAS patients, with the nomogram model demonstrating superior performance. Conclusion:The nomogram-based clinical prediction models developed in this study demonstrated robust performance in predicting long-term OS and RFS in patients with HAS.

Objective:This study aimed to analyze the prognostic risk factors for hepatoid adenocarcinoma of the stomach (HAS) and construct two nomogram-based clinical prediction models to predict overall survival (OS) and recurrence-free survival (RFS) in patients with HAS.Methods:Data were retrospectively collected from 82 patients (64 males, 18 females; mean age 60.3 ± 9.4 years) who underwent radical gastrectomy and were pathologically diagnosed with gastric hepatoid adenocarcinoma at the First Medical Center of the PLA General Hospital between February 2006 and September 2023. Statistical analyses were conducted using SPSS 25.0 and R 4.3.2. Survival analyses were performed using the Kaplan-Meier method, and univariate analyses were used to identify clinical and pathological factors associated with prognosis. Variables with P<0.05 in the univariate analysis were included in multivariate Cox regression models to identify independent risk factors for OS and RFS. These factors were incorporated into the prediction models to construct nomograms. The discriminatory power of the models was assessed using the area under the curve (AUC) of receiver operating characteristic (ROC) analyses, while calibration curves, decision curve analysis (DCA), and comparisons with the 8th edition of the TNM staging system of the American Joint Committee on Cancer (AJCC) were employed to evaluate model performance. Results:Among the 82 patients, 36 (43.9%) exhibited vascular infiltration, 61 (74.4%) had nerve infiltration, and lymph node metastasis was observed in 60 cases (73.2%). Pathological stages I, II, III, and IV were distributed as 11 (13.4%), 26 (31.7%), 44 (53.7%), and 1 (1.2%) cases, respectively. Inflammatory markers included neutrophil-to-lymphocyte ratio (NLR) ≥ 4.33 in 22 cases (26.8%), platelet-to-lymphocyte ratio (PLR) ≥ 142.2 in 50 cases (61.0%), monocyte-to-lymphocyte ratio (MLR) ≥ 0.411 in 22 cases (26.8%), α-fetoprotein (AFP) ≥ 2.48 μg/L in 64 cases (78.0%), and C-reactive protein (CRP) ≥ 7.506 mg/L in 12 cases (14.6%). Among the 82 patients, 3 cases (3.6%) were lost to follow-up. The median follow-up time was 52 (range: 8–147) months, with a median OS of 61(2–147) months. The 1-year and 3-year OS rates were 78.5% and 58.5%, respectively, while the 1-year and 3-year RFS rates were 77.3% and 60.3%, respectively. Multivariate analysis identified several independent risk factors influencing OS in patients with HAS: advanced pathological stage, MLR ≥ 0.411, AFP ≥ 2.545 μg/L, and CRP ≥ 7.51 mg/L. The hazard ratios (HRs) and 95% confidence intervals (CIs) were as follows: 5.218 (1.230–22.143), 2.610 (1.287–5.294), 2.950 (1.013–8.589), and 2.594 (1.145–5.877), respectively (all P < 0.05). For RFS, advanced pathological stage, PLR ≥ 152.0, and MLR ≥ 0.411 were independent risk factors, with HRs (95% CIs) of 4.735 (1.080–20.760), 3.759 (1.259–11.226), and 2.714 (1.218–6.048), respectively (all P < 0.05). The AUC values for OS prediction at 1 year, 3 years, and 5 years were 0.7765, 0.7525, and 0.7702, respectively. For RFS, the AUC values were 0.7304, 0.8137, and 0.8307 at 1 year, 3 years, and 5 years, respectively. The calibration curves demonstrated strong agreement between nomogram- predicted outcomes and observed survival data. DCA indicated that both TNM staging and the nomogram-based clinical prediction models provided a net positive benefit in predicting OS and RFS in HAS patients, with the nomogram model demonstrating superior performance. Conclusion:The nomogram-based clinical prediction models developed in this study demonstrated robust performance in predicting long-term OS and RFS in patients with HAS.

【Objective】 To establish and evaluate a fluorescent antibody to membrane antigen (FAMA) method for detecting antibodies against varicella-zoster virus (VZV) based on Vero E6 cells. 【Methods】 Based on the adapted VZV-Oka-E6 strain that VZV-Oka live attenuated varicella vaccine strain grew in Vero E6 cells, Vero E6 cells were infected with VZV-Oka-E6 of three different doses (10^4.65, 10^4.95 and 10^5.25 TCID50), and the cytopathic effect was observed under a microscope to determine the optimal infection dose of VZV-Oka-E6 strain. Then the detectable sensitivity of the infected cell antigen slides prepared after fixing the infected cells with different fixatives was compared to determine the optimal fixative. As a result, the FAMA method based on Vero E6 cells for the determination of neutralizing anti-VZV has been developed. The established FAMA assay was used to detect the international standard for varicella zoster immunoglobulin with different titers to determine the sensitivity of the assay. The specificity of the assay was evaluated by detecting specific antibodies against human herpes simplex virus (HSV) type 1 and type 2. The neutralizing anti-VZV antibodies of the international standard for varicella zoster immunoglobulin were detected using VZV-infected cell antigen slides prepared in the same batch and four different batches, respectively, to determine the intra-assay repeatability and inter-assay repeatability. The international standard for varicella zoster immunoglobulin with three known titers was detected to evaluate the relative accuracy of this assay. The anti-VZV titers in 20 apheresis plasma samples were determined with the newly established FAMA test and ELISA test, respectively, and the detection results of the two methods were compared using Spearman’s correlation test. 【Results】 The optimal infection dose of the VZV-Oka-E6 strain in FAMA assay was determined to be 10^5.25 TCID50, and acetone precooled at -20℃ was used as the fixative. The FAMA test has a high sensitivity with a detecting limit of 31.25 mIU/mL for neutralizing anti-VZV titers. The negative result was observed when detecting herpes simplex virus (HSV) type 1 and 2 specific antibodies. The international standard for varicella zoster immunoglobulin was detected by VZV infected cell antigen slides prepared in the same batch and 4 different batches, with the coefficient of variation being 29.95% and 26.71%, respectively. The detection value of the international standard for varicella zoster immunoglobulin with three different titer levels was consistent with their theoretical value. The correlation coefficient of the detection results of 20 apheresis plasma samples by the FAMA test and ELISA test was 0.268. 【Conclusion】 The VZV FAMA assay has good sensitivity, specificity, repeatability, and relative accuracy in detecting neutralizing anti-VZV titers. It can be applied for detecting neutralizing anti-VZV titers in apheresis plasma samples as well as the varicella-zoster immunoglobulin (VZIG) preparations.

Objective: To study the rapid antidepressant effects of cannabioiol(CBD) on depression-like mice and its possible mechanism. Methods: Chronic restraint was used to establish a mouse depression model. The test mice were divided into 5 groups: normal control group, model group, positive control group, CBD low-dose group (25 mg/kg) and CBD high-dose group(50 mg/kg). The mice in each group were given intragastric administration one hour before the behavioral experiment. After the behavioral experiment, the hippocampus and prefrontal cortex specimens were collected, and brain-derived neurotrophic factor(BDNF), postsynaptic density protein 95(PSD-95), synaptophysin(SYP) and target of rapamycin(mTOR) were tested by ELISA. Results: Compared with the model group, the central area activity distance percentage, the central area activity time percentage and total distance increased in the open field experiment in the CBD low-dose group. Compared with the model group, the percentage of immobility in the forced swimming experiment in the low-dose CBD group decreased. The ELISA test results showed that CBD could rapidly increase the concentration of BDNF and PSD-95 in the prefrontal cortex, as well as the concentration of SYP and mTOR in the hippocampus and prefrontal cortex. Conclusion CBD can rapidly improve the behavioral performance of depression-like mice, and rapidly up-regulate the level of BDNF and synaptic protein in the hippocampus or prefrontal cortex.

Every year more than 10 million people newly infected with Mycobacterium tuberculosis (MTB) worldwide, which seriously threats human health and life. The anti-MTB infection drugs are constantly developed and updated. Vitamin D3 is a drug which can regulate the immune system, its effect on MTB infection has attracted more and more attention. This article reviews the clinical efficacy of vitamin D3 in adjuvant therapy for MTB infection, and its mechanism in regulating the innate and adaptive immune system, to provide insight for treatment of MTB infection.

Objective: To detect 20 common deafness gene mutations in non-syndromic hearing loss patients in China using the melting curve method, and analyze and summarize the mutation data to explore the clinical value of this method. Methods: The real-time fluorescence PCR melting curve method was used to detect 20 common mutations of four deafness genes(GJB2,GJB3,SLC26A4 and mtDNA) in 492 patients with non-syndromic hearing loss recruited between March 2014 and September 2016 from the Otolaryngology Department of Xiangya Hospital, Central South University(283 males and 209 females, the age ranged from 1 to 48 years old). The Sanger sequencing method was used to compare the sensitivity, specificity, positive predictive value, negative predictive value, and total coincidence rate of the deafness mutation detected by the real-time fluorescence PCR melting curve method. Results: A total of 492 samples were detected. 193 wild-type samples, 93 homozygous mutant samples, 145 heterozygous mutant samples, 59 composite heterozygous mutant samples and 2 samples with unknown mutations were detected using the real-time fluorescence PCR melting curve method within the range of 20 gene mutations, whichwere identical to the Sanger sequencing results.The two samples were detected as unknown mutations by the real-time fluorescent PCR melting curve method were confirmed by Sanger sequencing, including a composite heterozygous mutant sample and a homogenous mutation sample. GJB2 c.235delC and SLC26A4 c.919-2 A>G were the most common hotspot mutations in this study, followed by mtDNA m.1555 A>G. Compared with the Sanger sequencing method, the sensitivity, specificity, positive predictive value, negative predictive value, and total coincidence rate of the real-time fluorescence PCR melting curve method were 100%, the Youden′s index was 1.0, and the Kappa value was 1. Conclusions The real-time fluorescence PCR melting curve method is suitable for the detection of deafness gene mutations. It has the advantages in terms of simple, rapid, high sensitivity and strong specificity and can accurately detect the 20 gene mutations of 4 common deafness genes in Chinese population, which is expected to be used for the clinical detection of deafness genes in the future.

Objective:To observe the dexmedetomidine by nasal drip on perioperative spinal surgery patients sedation and the effect of hemodynamic changes.Methods:90 ASA grade Ⅰ ～ Ⅲ,years 18 to 65,and in general anesthesia spinal surgery,and postoperative patients have to extube the endotracheal,were randomly divided into three groups:control group (group C),the dexmedetomidine 0.1 μg/kggroup (D1) and dexmedetomidine 1.5 μg/kggroup (D2),(n=30).Record into the OR (T0),before the induction (T1),1 min before intubation (T2),1 min after intubation (T3),start surgy (T4),began to stop general anesthetics (T5),1 min before extubation (T6),3 min after extubation (T7),and into the PACU (T8).The patient's heart rate (HR),mean arterial pressure (MAP),oxygen saturation (SPO2),finish operation from the general anesthetics toextube the endotracheal tube,stay time,patients in the postoperative recovery room Ramsay sedation scores.Results:Three groups of patients when T0 HR,MAP,SPO2,Ramsay sedation scores had no statistical difference (P≥ 0.05);Compared with group C,D1 and D2 group significantly lower each time point of HR,MAP,Ramsay sedation scores increase (P≤ 0.05),SPO2 no significant change (P≥ 0.05);Each time point compared with group D1,D2 group HR,MAP,significantly decreased,Ramsay sedation scores increase (P≤ 0.05),SPO2 no significant change (P≥ 0.05);D1 group HR,MAP,SPO2 at each time point,Ramsay sedation scores have no obvious difference (P≥ 0.05);D2 group HR,MAP,SPO2,Ramsay sedation scores significantly difference (P≥ 0.05).Group C T3,T4,T5,T6,T7 has each time point,T8 HR,MAP,up from T1,T2,Ramsay sedation scores were significantly improved (P≤ 0.05),SPO2 no significant change (P≥ 0.05).Conclusions:40 min before anesthesia induction dexmedetomidine by nasal drip can effectively inhibit intubation and extubation reaction,make the hemodynamic changes is more stable,and significantly reduce the incidence of patients with postoperative agitation.

ObjectiveTo assess the effectiveness and prognosis of different radical surgery for Hirschsprung disease (HD).MethodsThe bowel function of HD patients undergoing the anus modified Soave operation (84 cases,modified Soave group),modified Swenson operation (60 cases,modified Swenson group),modified Duhamel operation (76 cases,modified Duhamel group) was followed up by 3,6 months and 2 years after surgery.Long-term bowel function,clinical type,removal length,anorectal manometry,barium enema were analyzed and compared among three groups.ResultsThe occurrence rates of bowel dysfunction 3,6 months and 2 years after surgery in modified Soave group[17.9％(15/84),7.1％(6/84),4.8％ (4/84)] were significantly lower than those in modified Swenson group[41.7％ (25/60),21.7％(13/60),18.3％(11/60) ] and modified Duhamel group [ 36.8％ (28/76),18.4％ (14/76),13.2％(10/76) ].There was significant difference between modified Soave group and modified Swenson group,modified Duhamel group(P＜ 0.05 ).There was no significant difference between modified Swenson group and modified Duhamel group (P ＞ 0.05).When the removal length ≤35 cm,the occurrence rate of bowel dysfunction after surgery in modified Soave group [ 18.7％ (14/75)] was lower than that in improved Swenson group [ 39.5％ ( 17/43 ) ] and modified Duhamel group [ 34.4％ (21/61 ) ].There was significant difference between modified Soave group and modified Swenson group,modified Duhamel group (P ＜ 0.05).There was no significant difference between modified Swenson group and modified Duhamel group (P ＞ 0.05).When the removal length ＞ 35 cm,there was no significant difference in the occurrence rate of bowel dysfunction after surgery among three groups (P ＞ 0.05 ).The occurrence rates of bowel dysfunction in short-segment type and common type in modified Soave group was lower than those in modified Swenson group and modified Duhamel group.There was significant difference between modified Soave group and modified Swenson group,modified Duhamel group(P ＜ 0.05).There was no significant difference between modified Swenson group and modified Duhamel group (P＞ 0.05).The anorectal angle 2 years after surgery in modified Soave group [(93.67 ± 10.50)° ] was less than that in modified Swenson group [(110.20 ± 11.88)° ] and modified Duhamel group [(106.33 ± 12.21)° ].There was significant difference (P ＜0.05).ConclusionThe complication and trauma are significantly lower in the anus modified Soave operation than the modified Swenson operation and modified Duhamel operation,but the choice of surgery should be strictly controlled according to the anal HD treatment indications.